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PET Response-Guided Treatment of Hodgkin's Lymphoma: A Review of the Evidence and Active Clinical Trials.

ABSTRACT: Risk-adaptive therapy for Hodgkin's lymphoma focuses on treatment modifications based on assessment of response. [(18)F]Fluoro-deoxyglucose positron emission tomography (PET) performed during or after completion of chemotherapy is a strong prognostic factor for eventual treatment outcome. Conceptually, this strategy seeks to increase efficacy and minimize toxicity through the appropriate selection of patients for either therapy escalation (high-risk, PET positive) or de-escalation (low-risk, PET negative). Preliminary evidence with tailoring both chemotherapy (drug selection, number of cycles, and dose) and radiotherapy (omission or inclusion) is varied; however, numerous clinical trials seeking to validate this approach are ongoing. This paper summarizes the available evidence and active protocols involving PET response-adapted therapy for adult (early and advanced stages) Hodgkin's lymphoma.

SUBMITTER: Aridgides P

PROVIDER: S-EPMC3017897 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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PET Response-Guided Treatment of Hodgkin's Lymphoma: A Review of the Evidence and Active Clinical Trials.

Aridgides Paul P Bogart Jeffrey J Shapiro Anna A Gajra Ajeet A

Advances in hematology 20101227

Risk-adaptive therapy for Hodgkin's lymphoma focuses on treatment modifications based on assessment of response. [(18)F]Fluoro-deoxyglucose positron emission tomography (PET) performed during or after completion of chemotherapy is a strong prognostic factor for eventual treatment outcome. Conceptually, this strategy seeks to increase efficacy and minimize toxicity through the appropriate selection of patients for either therapy escalation (high-risk, PET positive) or de-escalation (low-risk, PET ...[more]

PMID: 21234382

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Project description:BackgroundWe tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma.MethodsPatients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points.ResultsA total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%.ConclusionsAlthough the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. (Funded by Cancer Research UK and Others; ClinicalTrials.gov number, NCT00678327.).

Project description:BACKGROUND:Standardized treatment in pediatric patients with Hodgkin's lymphoma (HL) follows risk stratification by tumor stage, erythrocyte sedimentation rate and tumor bulk. We aimed to identify quantitative parameters from pretherapeutic FDG-PET to assist prediction of response to induction chemotherapy. METHODS:Retrospective analysis in 50 children with HL (f:18; m:32; median age, 14.8 [4-18] a) consecutively treated according to EuroNet-PHL-C1 (n = 42) or -C2 treatment protocol (n = 8). Total metabolic tumor volume (MTV) in pretherapeutic FDG-PET was defined using a semi-automated, background-adapted threshold. Metabolic (SUVmax, SUVmean, SUVpeak, total lesion glycolysis [MTV*SUVmean]) and heterogeneity parameters (asphericity [ASP], entropy, contrast, local homogeneity, energy, and cumulative SUV-volume histograms) were derived. Early response assessment (ERA) was performed after 2 cycles of induction chemotherapy according to treatment protocol and verified by reference rating. Prediction of inadequate response (IR) in ERA was based on ROC analysis separated by stage I/II (1 and 26 patients) and stage III/IV disease (7 and 16 patients) or treatment group/level (TG/TL) 1 to 3. RESULTS:IR was seen in 28/50 patients (TG/TL 1, 6/12 patients; TG/TL 2, 10/17; TG/TL 3, 12/21). Among all PET parameters, MTV best predicted IR; ASP was the best heterogeneity parameter. AUC of MTV was 0.84 (95%-confidence interval, 0.69-0.99) in stage I/II and 0.86 (0.7-1.0) in stage III/IV. In patients of TG/TL 1, AUC of MTV was 0.92 (0.74-1.0); in TG/TL 2 0.71 (0.44-0.99), and in TG/TL 3 0.85 (0.69-1.0). Patients with high vs. low MTV had IR in 86 vs. 0% in TG/TL 1, 80 vs. 29% in TG/TL 2, and 90 vs. 27% in TG/TL 3 (cut-off, > 80 ml, > 160 ml, > 410 ml). CONCLUSIONS:In this explorative study, high total MTV best predicted inadequate response to induction therapy in pediatric HL of all pretherapeutic FDG-PET parameters - in both low and high stages as well as the 3 different TG/TL. TRIAL REGISTRATION:Ethics committee number: EA2/151/16 (retrospectively registered).

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PET Response-Guided Treatment of Hodgkin's Lymphoma: A Review of the Evidence and Active Clinical Trials.

Publications

PET Response-Guided Treatment of Hodgkin's Lymphoma: A Review of the Evidence and Active Clinical Trials.

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